International forskning

The impact of cannabidiol treatment on resting state functional connectivity, prefrontal metabolite levels and reward processing in recent-onset patients with a psychotic disorder


Ruben van Boxel 1, Shiral S Gangadin 2, Hella Janssen 1, Sanne van der Steur 1, Lucia J C van der Vinne 1, Lon Dortants 1, Teuntje A D Pelgrim 3, Luc W R Draisma 1, Ruth Tuura 4, Pim van der Meer 1, Albert Batalla 1, Matthijs G Bossong 5

  • 1Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
  • 2Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands; Section of Neuropsychiatry, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, the Netherlands.
  • 3Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands; Department of Psychiatry, Parnassia Psychiatric Institute, Amsterdam, the Netherlands.
  • 4Center of MR Research, University Children’s Hospital Zurich, Zurich, Switzerland.
  • 5Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands. Electronic address: m.bossong@hotmail.com.

Affiliationer

The first clinical trials with cannabidiol (CBD) as treatment for psychotic disorders have shown its potential as an effective and well-tolerated antipsychotic agent. However, the neurobiological mechanisms underlying the antipsychotic profile of CBD are currently unclear. Here we investigated the impact of 28-day adjunctive CBD or placebo treatment (600 mg daily) on brain function and metabolism in 31 stable recent-onset psychosis patients (<5 years after diagnosis). Before and after treatment, patients underwent a Magnetic Resonance Imaging (MRI) session including resting state functional MRI, proton Magnetic Resonance Spectroscopy (1H-MRS) and functional MRI during reward processing. Symptomatology and cognitive functioning were also assessed. CBD treatment significantly changed functional connectivity in the default mode network (DMN; time × treatment interaction p = 0.037), with increased connectivity in the CBD (from 0.59 ± 0.39 to 0.80 ± 0.32) and reduced connectivity in the placebo group (from 0.77 ± 0.37 to 0.62 ± 0.33). Although there were no significant treatment effects on prefrontal metabolite concentrations, we showed that decreased positive symptom severity over time was associated with both diminishing glutamate (p = 0.029) and N-acetyl-aspartate (NAA; neuronal integrity marker) levels (p = 0.019) in the CBD, but not the placebo group. CBD treatment did not have an impact on brain activity patterns during reward anticipation and receipt or functional connectivity in executive and salience networks. Our results show that adjunctive CBD treatment of recent-onset psychosis patients induced changes in DMN functional connectivity, but not prefrontal metabolite concentrations or brain activity during reward processing. These findings suggest that DMN connectivity alteration may be involved in the therapeutic effects of CBD.

Keywords: Anticipation; CBD; Default mode network; Glutamate; Psychosis; Schizophrenia.